Mousepox is a widely feared disease of mice caused by ectromelia virus. During most of the past decade, U.S. laboratory mice appeared to be free of mousepox, but this picture changed dramatically in 1979-80 when 8 separate research centers sustained outbreaks, particularly among colonies of inbred mice. Control of these costly epizootics relied on traditional measures - slaughter and vaccination - on the assumption that ectromelia virus is an irreversible hazard; an assumption not borne out by earlier studies in outbred mice and not systematically tested in inbred mice. Because inbred mice are so heavily used in biomedical research, critical gaps in knowledge about their responses to ectromelia virus must be filled to prevent unwarranted and potentially overzealous reactions to infection. To this end, the proposed research will: characterize the pathogenesis of mousepox in inbred mice resistant or susceptible to lethal infection, determine if mousepox infection can persist in an inbred host after sublethal or asymptomatic encounter with ectromelia virus; determine the relative importance of horizontal versus vertical transmission in the spread of infection, and study the effects of active and passive immunization on the epizootiology and pathogenesis of mousepox. Two prototype inbred strains, BALB/c and C57B/6 will be studied by a variety of morphological, virological, serological and epidemiological (including immunocytochemical) techniques after exposure to the NIH-79 strain of ectromelia virus; the strain isolated from recent U.S. epizootics. DNA hybridization probes prepared from vaccinia virus genome will be used to locate and quantitate ectromelia virus DNA in tissues. The results of this work will be used to develop marker criteria for predicting responses of mice to ectromelia virus and for reappraising approaches to the diagnosis and control of mousepox.